Compartmentalized IL-8 and Elastase Release Within the Human Lung in Unilateral Pneumonia

Abstract

Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and activating cytokine, we investigated IL-8 production in relation to neutrophil migration and elastase release in the human lung during unilateral community-acquired pneumonia (CAP). In 17 patients, the local response in the involved lung was compared with that in the contralateral, noninvolved lung, and with the systemic response. Eight healthy volunteers served as controls. IL-8, total neutrophil elastase (NE), free elastase activity, alpha 1-antitrypsin (alpha 1-AT), and total leukocyte and neutrophil counts were evaluated in bronchoalveolar lavage fluids (BALF). Mean IL-8 concentrations in BALF from the involved lungs of the patients were significantly greater than those in BALF from the noninvolved lung or from controls (p < or = 0.001). By contrast, the serum IL-8 concentration was not different in patients and in controls. Total NE and alpha 1-AT concentrations were increased in BALF from the involved lung as compared with the noninvolved lung or controls (p < or = 0.001). The elastase-inhibitory capacity of alpha 1-AT in BALF was impaired in the involved lung of seven of the 14 patients as compared with the controls, leading to free elastase activity in the involved lung of all patients with CAP. Plasma total NE concentrations were significantly greater in the CAP patients than in the controls. IL-8 concentrations in BALF correlated positively with total leukocyte counts, absolute numbers and percentages of neutrophils, total NE concentrations, and free elastase activity. Our results suggest that during unilateral CAP, locally produced IL-8 may trigger neutrophil accumulation and activation, thus contributing to a local elastase/antielastase imbalance within the site of infection.